Nutrient regulation of tissue stem cells

Stem cells renew our tissues, and they must be carefully controlled to secure tissue homeostasis.

For example, the intestinal epithelium undergoes constant turnover, which depends on the regulation of intestinal stem cell (ISC) proliferation and differentiation. Earlier studies have shown that Drosophila ISCs are a genetically tractable model to study the mechanisms that control tissue stem cells in vivo. Moreover, the ISCs respond to nutrient-induced cues, making this system an optimal model to address gene-nutrient interactions in stem cell control. On one hand, stem cells need to robustly sustain a metabolic profile that supports the stem cell identity. On the other hand, stem cells need to integrate nutrient-derived signals to dynamically control the cell cycle, self-renewal, and differentiation in order to match tissue function and repair with nutrient availability. Understanding stem cell specific metabolism and nutrient sensing may therefore provide new means to manipulate stem cell function, which can benefit the development of new therapies in longer perspective.

Our ongoing work on intestinal stem cells relies on genetic control of intestinal cell types, use of controlled dietary schemes to influence nutrient availability as well as cell imaging, transcriptomics and metabolomics. Through the close collaboration within the Center of Excellence in Stem Cell Metabolism (MetaStem) we will be able to test the conservation of our findings using mammalian stem cell models. Within MetaStem, we are also setting up a metabolomics platform, specifically designed for high sensitivity to allow analysis of metabolites from challenging stem cell and tissue samples.